Inherited Disorders
This lesson covers two key inherited disorders — cystic fibrosis and polydactyly — along with genetic screening, testing, and ethical considerations. This is essential content for Edexcel GCSE Biology (1BI0) Topic 3: Genetics.
Cystic Fibrosis
Cystic fibrosis (CF) is a genetic disorder caused by a recessive allele. It affects approximately 1 in 2,500 births in the UK.
Genetics of Cystic Fibrosis
- The allele for cystic fibrosis is recessive. We use f for the recessive (CF) allele and F for the dominant (normal) allele.
- A person must have two copies of the recessive allele (ff) to have cystic fibrosis.
- A person with one copy of the recessive allele (Ff) is a carrier — they do not have the disease but can pass the allele to their children.
| Genotype | Phenotype |
|---|
| FF | Unaffected (not a carrier) |
| Ff | Unaffected but a carrier |
| ff | Has cystic fibrosis |
Symptoms of Cystic Fibrosis
The faulty allele codes for a defective CFTR protein (cystic fibrosis transmembrane conductance regulator), which is a chloride ion channel. Normally, this protein transports chloride ions out of cells, and water follows by osmosis, keeping mucus thin and runny. When the protein is faulty:
- Thick, sticky mucus builds up in the lungs → makes breathing difficult and increases the risk of lung infections.
- Thick mucus blocks the pancreatic duct → prevents digestive enzymes from reaching the small intestine → difficulty digesting food (especially fats).
- Sticky mucus in the reproductive system → can cause fertility problems, especially in males.
Treatment of Cystic Fibrosis
- Physiotherapy — daily chest physiotherapy to loosen and clear mucus from the lungs.
- Antibiotics — to treat and prevent lung infections.
- Enzyme supplements — to help digest food (replacing the enzymes that cannot reach the intestine).
- Bronchodilators — to open the airways and make breathing easier.
- Gene therapy (experimental) — attempts to replace the faulty gene with a working copy.
Punnett Square for Cystic Fibrosis
Cross: Two Carriers (Ff × Ff)
This is the most commonly tested cross for cystic fibrosis.
Parental genotypes: Ff × Ff (both parents are carriers — unaffected but carrying one recessive allele).
Gametes:
- Parent 1: F or f
- Parent 2: F or f
Punnett Square:
Offspring:
| Genotype | Phenotype | Proportion |
|---|
| FF | Unaffected (not a carrier) | 1 in 4 (25%) |
| Ff | Unaffected carrier | 2 in 4 (50%) |
| ff | Has cystic fibrosis | 1 in 4 (25%) |
Key results:
- 3 out of 4 children (75%) will be unaffected.
- 1 out of 4 children (25%) will have cystic fibrosis.
- 2 out of 4 unaffected children (50% overall) will be carriers.
- Each child has a 1 in 4 (25%) chance of having cystic fibrosis.
Exam Tip: Both parents must be at least carriers (Ff) for a child to have cystic fibrosis. If one parent is FF, no children will have CF (though some may be carriers). The most commonly tested cross is Ff × Ff, giving the 3:1 ratio.
Polydactyly
Polydactyly is a genetic condition in which a person is born with extra fingers or toes (more than the usual 5 on each hand or foot). It is caused by a dominant allele.
Genetics of Polydactyly
- The allele for polydactyly is dominant. We use D for the dominant (polydactyly) allele and d for the recessive (normal) allele.
- A person only needs one copy of the dominant allele to have polydactyly.
- Polydactyly can be caused by either the homozygous dominant (DD) or heterozygous (Dd) genotype.
| Genotype | Phenotype |
|---|
| DD | Has polydactyly |
| Dd | Has polydactyly |
| dd | Normal number of digits |
Symptoms of Polydactyly
- The extra digit(s) may be fully formed with bones and joints, or may be small, fleshy nubs.
- Polydactyly can affect the hands, feet, or both.
- It is usually not harmful and is often treated by simple surgical removal of the extra digit(s).
Punnett Square for Polydactyly
Cross: Heterozygous Affected × Homozygous Normal (Dd × dd)
Parental genotypes: Dd (has polydactyly) × dd (normal)
Gametes:
- Parent 1 (Dd): D or d
- Parent 2 (dd): d only
Punnett Square:
Offspring:
| Genotype | Phenotype | Proportion |
|---|
| Dd | Has polydactyly | 2 in 4 (50%) |
| dd | Normal number of digits | 2 in 4 (50%) |
Key results:
- 1 in 2 (50%) chance of a child having polydactyly.
- 1 in 2 (50%) chance of a child having a normal number of digits.
- The ratio is 1:1 (1 polydactyly : 1 normal).
Exam Tip: Because polydactyly is dominant, only ONE affected parent is needed for children to potentially have the condition. Contrast this with cystic fibrosis, where BOTH parents must be carriers.
Comparing Cystic Fibrosis and Polydactyly
| Feature | Cystic Fibrosis | Polydactyly |
|---|
| Inheritance pattern | Autosomal recessive | Autosomal dominant |
| Allele notation | F (normal), f (CF) | D (polydactyly), d (normal) |
| Genotype of affected individual | ff (homozygous recessive) | DD or Dd (at least one dominant allele) |
| Can carriers exist? | Yes (Ff — unaffected carriers) | No — if you have the allele, you show it |
| Parents needed for affected child | Both parents must be carriers or affected (at least Ff) | Only one parent needs to be affected (Dd or DD) |
| Severity | Serious, life-limiting condition | Usually mild, correctable by surgery |
| Classic cross | Ff × Ff → 3:1 (3 unaffected : 1 affected) | Dd × dd → 1:1 (1 affected : 1 normal) |
Genetic Screening and Testing
Genetic testing involves analysing a person's DNA to look for specific alleles associated with genetic conditions.
Methods of Prenatal Genetic Testing
| Method | Description | When Performed | Risk |
|---|
| Amniocentesis | A needle is inserted through the abdomen into the amniotic fluid surrounding the foetus. A sample of fluid (containing foetal cells) is taken and the DNA is analysed. | From 15–20 weeks of pregnancy. | Small risk (about 1%) of miscarriage. |
| Chorionic villus sampling (CVS) | A small sample of tissue is taken from the placenta (chorionic villi), which has the same DNA as the foetus. The DNA is analysed. | From 10–13 weeks of pregnancy. | Slightly higher risk of miscarriage than amniocentesis (about 1–2%). |
Both methods can detect conditions such as cystic fibrosis and Down's syndrome before the baby is born.
Other Genetic Tests
- Carrier testing — tests adults to see if they carry a recessive allele for a genetic condition (e.g., CF). This is useful for couples planning a family who have a family history of a genetic condition.
- Pre-implantation genetic diagnosis (PGD) — used with IVF. Embryos are tested for genetic conditions before being implanted in the uterus. Only embryos without the condition are selected for implantation.
- Newborn screening — blood tests performed on all newborns (e.g., the heel prick test in the UK screens for conditions including CF and sickle cell disease).
Ethical Considerations
Genetic testing and screening raise important ethical questions:
Arguments For Genetic Testing
- Allows parents to prepare for a child with a genetic condition or make informed decisions about the pregnancy.
- Carrier testing allows couples to assess the risk before having children.
- PGD can prevent children being born with serious genetic conditions.
- Early detection through newborn screening allows early treatment, improving outcomes.
- Can inform family members that they may also be carriers.
Arguments Against Genetic Testing
- Results may cause anxiety and stress, even if the condition may never develop.
- Risk of miscarriage from amniocentesis and CVS.
- Some people believe selecting embryos (PGD) is a form of "designer babies" or eugenics.
- Insurance and employment discrimination — people with certain genetic results could face discrimination.
- The decision to terminate a pregnancy based on genetic test results raises moral and religious concerns.
- Results are not always 100% accurate — false positives or negatives can occur.
- Privacy concerns — who has access to genetic information?